Molecular Mimicry between Meningococcal B Factor H-Binding Protein and Human Proteins

This study calls attention on molecular mimicry and the consequent autoimmune cross reactivity as the molecular mechanism that can cause adverse events following meningococcal B vaccination and warns against active immunizations based on entire antigen.


Introduction
The bacterium Neisseria meningitides (aka meningococcus) can cause a multitude of severe illnesses, collectively termed meningococcal disease. 1 Numerous vaccines are available and, among them, a meningococcal B vaccine (namely, Trumenba) has been approved for children and contains the lipoprotein factor H-binding protein (fHbp). 2 Indeed, as described by Seib et al, 3 preclinical studies demonstrated that fHbp elicits a robust bactericidal antibody response that correlates with the amount of fHbp expressed on the bacterial surface.However, according to the vaccine-prescribing informations, 4 numerous adverse events occur following fHbp vaccine administration.That is, verbatim: • Immune system disorders.
Currently, at the best of the author's knowledge, no investigation/hypothesis has been proposed to define the molecular mechanism that triggers the adverse events following the Trumenba vaccine administration.In analyzing the issue, this study posed the question of whether molecular mimicry between the vaccine antigen and the human proteins might play a role as already found in analogous research models. 5,6

Materials and Methods
Molecular mimicry between the bacterial fHbp antigen and human proteins was analyzed according to published methodology. 5,6In brief, the fHbp antigen, 274 amino acids (aa) as described at https://www.uniprot.org/uniprotkb/Q9JXV4/,was dissected into pentapeptides offset each other by one aa residue (i.e., MNRTA, NRTAF, RTAFC, and so forth) and the resulting bacterial pentapeptides were analyzed for occurrences within the human proteome.
][9][10] Peptide match and peptide search programs available at www.uniprot.org 11were used.multiple occurrences in human protein alterations which can lead to severe diseases.The bacterial versus human pentapeptide overlap is of such a dimension that obviously it cannot be reported in the context of an article.Consequently, data are reported as ►Supplementary Table S1 that is a fundamental part of this report.
In parallel, the severe diseases  that could derive from the massive molecular mimicry and consequent crossreactivity and autoimmunity are numerous. Here,only a short synopsis that gives an overview of such diseases is given in ►Table 1, thus confirming the vaccine-induced injuries listed in the Trumenba vaccine-prescribing informations.4

Conclusion
The vast sharing of immune peptide determinants between the bacterial fHbp antigen and the human proteins warns against Trumenba utilization to prevent meningococcal diseases.Indeed, the present data speak for themselves and clearly predict a very high incidence of autoimmune pathologies in the vaccinees as a result of molecular mimicry and the consequent potential cross-reactivity, thus factually confirming what had already been stated in the prescribing information of the Trumenba vaccine. 4n synthesis, this report adds to numerous previous studies, [5][6][7][8][9][10] and further references therein, that explicated Table 1 Peptides shared between fHbp protein and human proteins that-when altered-are associated with myelination, neuropathy, myopathy, ataxia, etc.

Peptides a
Human proteins: name and associated diseases Molecular Mimicry between fHbp and the Human Proteome Kanduc how only vaccinal protocols based on peptide sequences uniquely present in the pathogenic antigens can provide therapeutic vaccines free of adverse events.Molecular Mimicry between fHbp and the Human Proteome Kanduc 313

Table 1 (
Continued) Further disease details are available in OMIM, PubMed, and UniProt databases.
Abbreviation: fHbp, factor H-binding protein.a Hexapeptides formed by overlapping pentapeptides have been underlined.b Human protein names are given in italic.c Global Medical Genetics Vol. 10 No. 4/2023 © 2023.The Author(s).